The major aim of this research proposal is to define antigens associated with adenocarcinoma of the pancreas with monoclonal antibody and to use these reagents as immunological probes for the development of new approaches that may prove useful for the treatment of pancreatic cancer. The specific aims desinged to achieve this objective are 1) to develop murine monoclonal antibodies to pancreatic carcinoma associated antigens, 2) to identify monoclonal antibodies directed preferentially against such antigens by reacting hybridoma supernatants with a) cultured cell lines derived from metastatic and primary lesions of pancreatic carcinoma, b) cell lines derived from a variety of other neoplasms, c) cultured human lymphoblastoid cells, and d) freshly explanted neonatal pancreatic tissues; 3) to establish some of the immunochemical and molecular characteristics of molecules bearing antigenic determinants recognized by the monoclonal antibodies, and 4) to critically evaluate in an animal model system in athymic (nu/nu) mice the effect of specific monoclonal antibodies on immune killing and growth characteristics of pancreatic carcinoma cells. In this regard, attempts will be made to detect tumor markers in the circulation of nude mice bearing human pancratic tumors and to correlate their presence with tumor volume. It is anticipated that information obtained from the proposed studies may add to our understanding of the molecular and cellular mechanisms involved in interactions of tumor cells with the host's immune system and will thus contribute to progress in the attack on pancreatic cancer.